Kindling and associated mossy fibre sprouting are not affected in mice deficient of NGFI-A/NGFI-B genes.
Kindling is an animal model of epileptogenesis, whereby repeated administration of an initially subconvulsive electrical stimulation eventually leads to the development of generalized motor seizures. Once established, the kindling effect is permanent. Although the molecular basis of kindling remains incompletely understood, emerging lines of evidence suggest that the induction of immediate-early genes could represent a link between periodic short-term stimuli and the long-lasting functional and structural alterations in the brain associated with the development of seizures. A recent study showed that null mutation of the immediate-early gene c-fos impairs the structural and functional plasticities in kindling. In the present study, we examined whether two other seizure-inducible immediate-early genes--NGFI-A (also termed EGR-1, zifl268, and Krox-24) and NGFI-B (also termed Nur77)--play requisite roles in kindling. We found that neither the rate of kindling nor seizure-induced granule cell axonal sprouting was affected in mice carrying a null mutation of NGFI-A. Furthermore, double knock-out of NGFI-A and NGFI-B genes does not result in detectable changes in kindling development and associated mossy fibre sprouting. Taken together, our observations indicate that neither constitutive nor seizure-induced expression of NGFI-A or NGFI-B is uniquely required for the establishment of kindling. These findings underscore the specificity of the immediate-early genes whose transcriptional activation contributes to kindling epileptogenesis.
Zheng
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D
Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.
Butler
L S
LS
McNamara
J O
JO
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D017781:Genes, Immediate-Early / Q000502:physiology; D006651:Histocytochemistry; D017874:Immediate-Early Proteins; D007696:Kindling, Neurologic / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors